Oxygen free radicals have been widely postulated to play a causal role in the aging process of animals. The main objective of the proposed investigation is to understand the relationship between oxygen free radicals, generated in mitochondria, and the cellular aging process, using the common housefly, Musca domestica, as an experimental model. It will be ascertained if the rate of oxygen free radical generation is associated with the physiological or the chronological rate of aging. Distinction between the physiological and the chronological age of animals will be made by: (1) Selection of flies with a predisposition to undergo accelerated senescence and an earlier death than their cohorts of the same chronological age. (2) Experimental manipulation of life spans by varying the rates of metabolic expenditure. Life span of the housefly is inversely related to metabolic rate. The average and the maximum life span can be prolonged approximately two-fold by restriction of the flight activity. Oxygen free radical production will be measured as rates of superoxide radical (O-2) and hydrogen peroxide (H2O2) generation in isolated mitochondria and in tissue homogenates. Rates of O-2 and H2O2 production will be compared between flies undergoing varied rates of aging. Results of this study should indicate if the rates of O-2 and H2O2 production by mitochondria correspond to the physiological or the chronological age of the animals. An additional goal of this study is to understand the underlying cause of age-related changes in O-2 generation by mitochondria. The hypothesis that lipid peroxidation damage may alter the rate of O-2 production by affecting electron flow or the autoxidizable content of ubiquinone will be tested. A novel aspect of this study is that its design allows modification of the rate of aging whereby a distinction can be drawn between the physiological and the chronological age. In addition, organisms with shorter- and longer-life expectancies can be identified in cohort populations. By comparison of animals of similar chronological but different physiological age, and vice versa, the specificity of a biological parameter to the aging process can be tested. The potential usefulness of this study lies in the identification of physiologically-significant cellular alterations which are associated with mortality rates and life expectancy of organisms.